The present invention relates generally to immunointeractive molecules and their use inter alia in the detection and/or purification of T-cell antigen binding molecules (TABMs). These molecules are also called T-cell derived antigen binding molecules. The ability to determine the presence and levels of particular TABM provide a useful diagnostic monitoring procedure for a variety of disease or other physiological conditions which are associated directly or indirectly with TABM including a range of allergies, immunological status, immunological dysfunction, neuropeptide release, infection, cancer, autoimmune disease or vaccination status. The immunointeractive molecules of the present invention are also useful in a range of conditions including modulating aspects of an immune response such as but not limited to cell mediated immunity.
Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description.
The rapidly increasing knowledge of the immune system is greatly facilitating the rationale design of therapeutic and diagnostic procedures based on modulating aspects and compounds of the immune system. Our understanding of the immune system is predicated in part on the identification and characterization of immune system components and determining how various components interact. Although a substantial focus of the research over the years has been on studying immunoglobulins, other immunointeractive molecules such as TABM have received less attention. This has been due, in part, to the inability to purify large amounts of these immunointeractive molecules.
TABM are antigen binding molecules generally located in the serum, derived from T-cells TABM can be regarded as immunoproteins which are antigen specific and, hence, are analogous to immunoglobulins.
TABM are, however, distinct from immunoglobulins. For example, TABM recognise different epitopes to immunoglobulins. TABM are present in serum in multimetric form, the monomer having an apparent molecular weight on a 10-15% w/v SDS polyacrylamide gel of about 24,000-30,000 daltons. In polymeric form, the molecular weight may be greater than 1,000,000 daltons. The high molecular weight of TABM and their non-polar, hydrophobic nature have made the study of these molecules very difficult.
TABM are present in the serum at a concentration of between 10-50 xcexcg/ml. The monomeric units share some homology with the Cxcex1 chain of the T-cell receptor (TCR). However, TABM are not soluble forms of TCR and exhibit physiological and biochemical properties distinct from TCR.
There appears to be several types of TABM with different functions. One particularly important function is their involvement in immuno-regulation. For example, some TABM initiate delayed type hypersensitivity while other types appear to inhibit cell-mediated immunity. The latter type of TABM are associated with cytokines and in particular interleukin 10 (IL-10) and transforming growth factor beta (TGF-xcex2). It is thought that these TABM xe2x80x9cfocusxe2x80x9d the cytokines to where the antigen is localised to suppress the cell-mediated immune response to the antigen.
It is likely, therefore, that TABM are involved in a number of clinical disorders or others physiological conditions involving suppression or activation of immune processes. However, as TABM are present in serum in only minute amounts, it has hithertofore been impractical to measure TABM levels or to use TABM in diagnostic protocols.
In work leading up to the present invention, the inventors sought monoclonal antibodies to TABM. The isolation of such monoclonal antibodies enables the purification of large quantities of TABM and the development of diagnostic assays based on identification of specific TABM or amounts of specific TABM as well as the development of therapeutic protocols based on modulating TABM levels.
Throughout this specification, unless the context requires otherwise, the word xe2x80x9ccomprisexe2x80x9d, or variations such as xe2x80x9ccomprisesxe2x80x9d or xe2x80x9ccomprisingxe2x80x9d, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
One aspect of the present invention provides an immuno-interactive molecule comprising a portion which is capable of specifally interacting with TABM.
Another aspect of the present invention is directed to a hybridoma cell line producing a monoclonal antibody comprising a binding portion specific to TABM.
Yet another aspect of the present invention contemplates a hybridoma cell line having the characteristics of cell line MG3C9-1A12 producing a monoclonal antibody capable of interacting with TABM.
Cell line MG3C9-1A12 was deposited under the provisions of the Budapest Treaty with the American Type Culture Collection, 10801 University Boulevard, Manassas, Va. 20110-2209 on Oct. 21, 1998. Accession No. HB-12589 was assigned to this deposited cell line.
Still yet another aspect of the present invention contemplates a method of detecting TABM in a biological sample from a subject said method comprising contacting said biological sample with an immunointeractive molecule specific for TABM or their derivatives or homologues for a time and under conditions sufficient for an immunointeractive molecules-TABM complex to form and then detecting said complex.
Another aspect of the present invention provides a composition comprising an immunointeractive molecules specific for TABM.
Yet another aspect of the present invention contemplates a method for determining assessing or otherwise monitoring the immunological status of an individual said method comprising screening for the pressure or level of TABM in a biological sample from said individual.